Evaluation of iron oxide nanoparticle micelles for Magnetic Particle Imaging (MPI) of thrombosis

Abstract

Magnetic particle imaging (MPI) is an emerging medical imaging modality that directly visualizes magnetic particles in a hot-spot like fashion. We recently developed an iron oxide nanoparticle-micelle (ION-Micelle) platform that allows highly sensitive MPI. The goal of this study was to assess the potential of the ION-Micelles for MPI-based detection of thrombi. To this aim, an in vivo carotid artery thrombosis mouse model was employed and ex vivo magnetic particle spectrometer (MPS) measurements of the carotid arteries were performed. In addition, we studied the effect of functionalization of the ION-Micelle nanoplatform with fibrin-binding peptides (FibPeps) with respect to nanoparticle thrombus uptake and hence thrombus detection. In vivo quantitative MR imaging pre- and post-ION-Micelle injection was performed as reference for visualization of ION-micelle uptake. ION-Micelles significantly decreased T 2 values in the thrombi with respect to pre-injection T 2 values (p <0.01) and significantly increased ex vivo MPS thrombus signal with respect to the noninjured, contralateral carotid (p < 0.01). Functionalization of the ION-Micelles with the FibPep peptides did not result in an increased MPS thrombus signal with respect to the non-fibrin binding ION-Micelles. The lack of a significant increased thrombus uptake for the FibPep-ION-Micelles indicates that (non-fibrin-specific) entrapment of nanoparticles in the meshlike thrombi is the key contributor to thrombus nanoparticle uptake. Therefore, (nontargeted) ION-Micelles might be of value for noninvasive MPI-based diagnosis, characterization and treatment monitoring of thrombosis.